GLP-1 is an incretin hormone that is released postprandially. GLP-1 has multi-faceted actions, including glucose-induced stimulation of insulin biosynthesis and secretion, inhibition of glucagon secretion, regulation of gene expression, trophic effects on 13 cells, inhibition of food intake, and slowing of gastric emptying. These effects contribute to the normalisation of elevated blood glucose, as well as to the control of satiety and body weight. GLP-1 has been shown to reduce postprandial and fasting glycaemia in subjects with type 2 diabetes mellitus and may therefore be a potentially useful new therapeutic agent in the treatment of type 2 diabetes mellitus. Moreover, GLP-1 could be used to increase satiety and also to prevent and treat obesity.
GLP-1 is related in sequence to GLP-2, glucagon, GIP (Gastric Inhibitory Polypeptide or Glucose-dependent Insulinotropic Polypeptide) and other members of the glucagon peptide superfamily. Many of these peptides exhibit an alanine at position 2, rendering them substrates for degradation by the enzyme dipeptidyl peptidase IV (DPP-IV). Indeed, GLP-1 is rapidly degraded in plasma and therefore has a very short half-life of about 1-2 min. DPP-IV is a multifunctional transmembrane glycoprotein that contains N-terminal dipeptidase activity, which is present on most mammalian cells, in a variety of tissues such as liver, kidney, small intestine, salivary gland, blood cells and plasma. Inhibition of DPP-IV will result in prolongation of the circulating half-life of GLP-1, such that GLP-1 levels increase as to be able to act as a therapeutic agent.
WO 01/37850 describes the stimulating effect of casein glycomacropeptide (CGMP) obtained by rennet hydrolysis of milk (single cleavage of K-casein) on the GLP-1 release in an intestinal cell line. EP 1367065 discloses the use of acid-soluble proteins from micellar casein for increasing GLP-1 or GLP-2 secretion.
WO2004/002241 describes the use of undefined whey proteins and whey protein hydrolysates, in particular α-lactalbumin and β-lactoglobulin hydrolysates, capable of inducing cellular release of GLP and CKK.
Proteins, in particular milk proteins, are commonly known as precursors of a range of biologically active peptides. The fact that proteins are precursors of biologically active molecules is particularly attractive for the development of functional foods, such as foods that may aid in any of the above GLP-1 mediated conditions. Food protein hydrolysates are well-used food ingredients and are of natural origin, such that no synthetic ingredients are required for obtaining the functional effect, in casu stimulation of secretion of GLP-1 and inhibition of its degradation so as to prevent or treat GLP-1 mediated conditions such as obesity, type 2 diabetes mellitus and immunological disorders.
Thus, it is desired to provide protein hydrolysates that are enriched in peptides that stimulate the secretion GLP-1 and optionally inhibit DPP-IV activity, such that they may aid in prevention and treatment of the above-identified GLP-1 mediated conditions. It was found that protein hydrolysates, such as e.g. milk protein hydrolysates could be used for stimulating GLP-1.